Procedural Learning among HIV+ and HIV- individuals with Substance Dependence
R. Gonzalez, J. Jacobus, J.W. Rodriguez,
E.H. Fakhoury, E.M. Martin
Brief Background
• HIV is associated with striatal damage
• Substance use affects striatal systems
• Striatum is critical for procedural learning
• Procedural learning in HIV & substance use – A. Martin et al., (1993)– Kalechstein et al., (1998)– Van Gorp et al., (1999)– Waldrop et al., (2001)
PL Measures
Pursuit Rotor (PR)
• Trace star seeing only mirror image– Go quickly, stay inside lines
– 4 trial blocks, 2 trials each
– DV = time to complete
• Follow light around circle– 55 rpm
– 4 trial blocks, 2 20s trials each
– DV = seconds on target
Mirror Tracing (MT)
Weather Prediction (WP)
• Try to guess “sun” or “rain” based on cards – Participants are not told probability structure
– 4 trial blocks, 50 cards each
Performance on PL Tasks
Performance Indices
| General Deficit(Main Effect)
| PL Deficit(Group X Time)
| # Errors
Time (Trial Blocks)
Per
form
ance
Control Group
Clinical Group
Lea
rnin
g
Hypotheses
• HIV+ participants:– poorer performance, overall, on measures of PL
• General Deficit
– less improvement in performance over time on PL tasks• PL Deficit
• More severe substance use:– poorer performance overall and with poorer PL
• Interaction between HIV and substance use
Participants
• 79 adults with history of cocaine and/or heroin dependence– HIV- : n = 33– HIV+: n = 46
• Negative u-tox & alcohol breath test
• No cocaine or heroin use in last 7 days
• No current abuse or dependence for EtOH and other drugs
• No history of severe thought disorder or unmedicated bipolar disorder
• No history of significant loss of consciousness or neurological problems
Demographics HIV – (n = 33) HIV + (n = 46)
Age 45.8 (7.9) 44.2 (6.6) yrs of education 12.3 (1.8) 11.9 (1.7) AmNART 102.6 (9.3) 100.6 (7.6) % men 87.9% 71.7% Ethnicity/Race Caucasian 9% 2% Hispanic 3% 5% African American 88% 91% Other 0 2%
Psychiatric & Medical HIV – (n = 33) HIV + (n = 46) BDI-2 12 (10.6) 14 (12.6) STAI 38.8 (13.3) 37.7 (13.5) WURS 32.8 (19.1) 30.6 (16.6) % on psych meds 21% 36% HCV+ 30% 43% On methadone 36% 4% CD4 | 396 (206) %AIDS (CD4) | 16% plasma viral load (Md, IQR) | 399 [75, 4970] % detectable viral load | 58% on HAART | 48%
Substance Use Parameters
HIV – (n = 33) HIV + (n = 46) yrs drug use 22.5 (9.1) 22.0 (8.7) dys since last use 120 [64, 263] 182 [86, 373] History of SCID-SAM Dx Alcohol 88% 91% Cocaine 91% 96% Heroin 79% 46% Cannabis 94% 72% Stimulants 7% 24% Hallucinogens 10% 24% Sedatives 17% 29% Injection drug use 42% 46% KMSK (peak) Cocaine + Heroin M, SD 19.5 (6.2) 18 (5.6) Md, Range 19 [6, 29] 16 [9, 28] dys since peak use (Md, IQR) 1095 [240, 2980] 1095 [365, 2351]
Summary of Results
Pursuit Rotor Mirror Tracing Weather Prediction Main Effects HIV .16 < .01 .12 KMSK ns ns ns Time < .01 < .01 ns Interactions HIV x KMSK ns ns ns HIV x Time ns ns ns KMSK x Time ns .08 ns HIV x KMSK x Time .03 .01 .10
5
7
9
11
13
15
Block 1 Block 2 Block 3 Block 4
Pursuit Rotor
se
co
nd
s
HIV- HIV+
10
12
14
16
18
20
22
24
Block 1 Block 2 Block 3 Block 4
Mirror Tracing
se
co
nd
s
HIV- HIV+
Mirror Tracing HIV Main Effect: Hedges ES = 0.65, 95%CI [0.20, 1.11]Significant 3-way interactions
25
27
29
31
33
Block 1 Block 2 Block 3 Block 4
Weather Prediction
# c
orr
ec
t
HIV- HIV+
PR Interaction Effect
-4
-2
0
2
4
6
8
10
12
PR
4/4-
PR
1/1
5 10 15 20 25 30KMSKpeak-tobalcmj
-4
-2
0
2
4
6
8
10
12
PR
4/4-
PR
1/1
5 10 15 20 25 30KMSKpeak-tobalcmjKMSK KMSK
PR
ch
an
ge
PR
ch
an
ge
HIV – HIV +
n = 33 n = 46R2 = .16, p = .02 R2 = .03, p = .24
↑ improvement in PR was associated with history of ↑ severe drug use[only for HIV- subjects]
0
5
10
15
20
ST
Mt1
/4-4
/4
5 10 15 20 25 30KMSKpeak-tobalcmj
MT Interaction Effect
0
5
10
15
20
ST
Mt1
/4-4
/4
5 10 15 20 25 30KMSKpeak-tobalcmj
HIV – HIV +
n = 33 n = 46R2 = .12, p = .05 R2 = .03, p = .26
KMSK
MT
ch
an
ge
MT
ch
an
ge
↑ improvement in MT was associated with history of ↑ severe drug use [only for HIV- subjects]
KMSK
Summary• HIV+ subjects generally performed worse,
overall, on PL tasks– Significant differences on Mirror Tracing– Evidence suggests general deficit
• History of substance use severity and HIV serostatus interacted to affect procedural learning
Possible Explanations• Supersensitivity of striatal dopamine receptors
– Process disrupted by HIV
• HIV+ participants fairly “healthy”
• Control group consisted of individuals with substance dependence
• Amount of striatal damage not sufficient for functional deficits
• HIV deficits are “spotty” affecting multiple systems
Acknowledgements• NIDA
– F32 DA018522 (RG)– R01 DA12828 (EMM)
• University of Illinois Chicago, Dept. of Psychiatry
• HIV & Addictions Neuroscience– Eileen Martin, PhD– Jasmin Vassileva, PhD– Pyrai Vaughn– Elizabeth Walczak– Leslie Ladd– Sarah Wicks